The UNC5C netrin receptor regulates dorsal guidance of mouse hindbrain axons.
The UNC5C netrin receptor regulates dorsal guidance of mouse hindbrain axons.
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DOI：
10.1523/jneurosci.5254-10.2011
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发表时间：
2011-02-09
期刊：
影响因子：
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通讯作者：
Ackerman SL
中科院分区：
文献类型：
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作者：
Kim D;Ackerman SL
小脑从位于脑干的多个小脑前核接受输入，并通过小脑深部神经元将处理后的信息发送到其他大脑结构。已经确定了调节小脑前神经元复杂迁移的指导分子及其主导过程的初步指导。然而，小脑前轴突背侧引导至发育中的小脑，或引导深核交叉轴突所需的分子尚不清楚。为了确定Unc5c是否在小脑前和小脑深部轴突的背侧引导中发挥作用，我们研究了Unc5c-/-小鼠这些神经元的轴突轨迹。我们的结果表明，Unc5c广泛表达于小脑前神经元和小脑深部神经元。在穿过中线后，Unc5c缺失扰乱了下橄榄和桥脑轴突的远距离背侧引导。此外，在Unc5c-/-小鼠中，来自小脑内侧深部神经元和外楔状神经元的轴突的背侧引导受到影响，桥脑神经元的前迁移也受到影响。Unc5c-/-小鼠与其轴突引导缺陷相一致，观察到楔状外核和下橄榄核神经元变性。最后，Atoh1启动子在深部神经元和桥脑神经元中的转基因表达挽救了在Unc5c-/-胚胎中观察到的小脑内侧深部轴突和桥脑轴突的缺陷，表明Unc5c在这些轴突的引导下自主地发挥细胞作用。我们的结果表明，Unc5c在发育中的后脑轴突的背侧引导中发挥着广泛的作用。
The cerebellum receives its input from multiple precerebellar nuclei located in the brainstem, and sends processed information to other brain structures via the cerebellar deep neurons. Guidance molecules that regulate the complex migrations of precerebellar neurons and the initial guidance of their leading processes have been identified. However, the molecules necessary for dorsal guidance of precerebellar axons to the developing cerebellum, or for guidance of decussating axons of the deep nuclei are not known. To determine whether Unc5c plays a role in the dorsal guidance of precerebellar and deep cerebellar axons, we studied axonal trajectories of these neurons in Unc5c-/- mice. Our results show that Unc5c is expressed broadly in the precerebellar and deep cerebellar neurons. Unc5c deletion disrupted long-range dorsal guidance of inferior olivary and pontine axons after crossing the midline. In addition, dorsal guidance of the axons from the medial deep cerebellar and external cuneate neurons was affected in Unc5c-/- mice, as were anterior migrations of pontine neurons. Coincident with the guidance defects of their axons, degeneration of neurons in external cuneate nucleus and subdivisions of inferior olivary nucleus was observed in Unc5c-/- mice. Lastly, transgenic expression of Unc5c in deep neurons and pontine neurons by the Atoh1 promoter rescued defects of the medial deep cerebellar and pontine axons observed in Unc5c-/- embryos, demonstrating that Unc5c acts cell autonomously in the guidance of these axons. Our results suggest that Unc5c plays a broad role in dorsal guidance of axons in the developing hindbrain.